Protein Targeting and Mutations

8/11/2019 Protein Targeting and Mutations

1/13

Copyright 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Polyribosomes

A number of ribosomes can translate a single

mRNA molecule simultaneously

Forming a polyribosome

Figure 17.20a, b

Growing

polypeptides

Completed

polypeptide

Incoming

ribosomal

subunits

Start of

mRNA

(5end)

End of

mRNA

(3end)

An mRNA molecule is generally translated simultaneously

by several ribosomes in clusters called polyribosomes.

(a)

Ribosomes

mRNA

This micrograph shows a large polyribosome in a prokaryotic

cell (TEM).

0.1 m

(b)


2/13



3/13



4/13


Completing and Targeting the Functional Protein

Polypeptide chains

Undergo modifications after the translationprocess


5/13


Protein Folding and Post-Translational Modif ications

After translation

Proteins may be modified in ways that affecttheir three-dimensional shape


6/13


Proteins destined for the endomembrane

system or for secretion Must be transported into the ER

Have signal peptides to which a signal-

recognition particle (SRP) binds, enabling thetranslation ribosome to bind to the ER



Figure 17.21

Ribosome

mRNA

Signal

peptide

Signal-

recognition

particle

(SRP) SRP

receptor

protein

Translocation

complex

CYTOSOL

Signal

peptide

removed

ER

membrane

Protein

ERLUMEN

The signal mechanism for targeting proteins to

the ERPolypeptide

synthesis begins

on a free

ribosome in

the cytosol.

1 An SRP binds

to the signal

peptide, halting

synthesis

momentarily.

2 The SRP binds to a

receptor protein in the ER

membrane. This receptor

is part of a protein complex

(a translocation complex)

that has a membrane pore

and a signal-cleaving enzyme.

3 The SRP leaves, and

the polypeptide resumes

growing, meanwhile

translocating across the

membrane. (The signal

peptide stays attached

to the membrane.)

4 The signal-

cleaving

enzyme

cuts off the

signal peptide.

5 The rest of

the completed

polypeptide leaves

the ribosome and

folds into its final

conformation.

6



Mutations

The change of a single nucleotide in the DNAs template strand

Leads to the production of an abnormal protein

Caused by radiation, viruses, mutagenic chemicals (Mutagens)

Spontaneous mutations : can occur during DNA replication, recombination, repair

Figure 17.23

In the DNA, the

mutant template

strand has an A where

the wild-type template

has a T.

The mutant mRNA has

a U instead of an A in

one codon.

The mutant (sickle-cell)

hemoglobin has a valine

(Val) instead of a glutamic

acid (Glu).

Mutant hemoglobin DNAWild-type hemoglobin DNA

mRNA mRNA

Normal hemoglobin Sickle-cell hemoglobin

Glu Val

C T T C A T

G A A G U A

3 5 3 5

5 3

5

3



Types of Point Mutations

Point mutations within a gene can be divided

into two general categories Base-pair substitutions

Base-pair insertions or deletions



Substitutions

A base-pair substitution

Is the replacement of one nucleotide and itspartner with another pair of nucleotides

Can cause missense or nonsense

Figure 17.24

Wild type

A U GA A G U U U G G C U A AmRNA 5Protein Met Lys Phe Gly

Stop

Carboxyl endAmino end

3

A U G A A G U U U G G U U A A

Met Lys Phe Gly

Base-pair substitution

No effect on amino acid sequenceU instead of C

Stop

A U G A A G U U U A G U U A A

Met Lys Phe Ser Stop

A U G U A G U U U G G C U A A

Met Stop

Missense A instead of G

NonsenseU instead of A

Silent : same amino acid

Missense: Different amino acid

Nonsense: stop and truncate a protein



I nsertions and Deletions

Insertions and deletions

Are additions or losses of nucleotide pairs in a gene

May produce frameshift mutations

Figure 17.25

mRNA

Protein

Wild type

A U G A A G U U U G G C U A A5

Met Lys Phe Gly

Amino end Carboxyl end

Stop

Base-pair insertion or deletionFrameshift causing immediate nonsense

A U G U A A G U U U G G CU A

A U G A A G U U G G C U A A

A U G U U U G G C U A A

Met Stop

U

Met Lys Leu Ala

Met Phe GlyStop

MissingA A G

Missing

Extra U

Frameshift causing

extensive missense

Insertion or deletion of 3 nucleotides:

no frameshift but extra or missing amino acid

3


13/13

Documents

Protein Targeting and Mutations